Decades of research have failed to elucidate the etiology of ulcerative colitis. A recent development is the carrageenan animal model which now permits experimental studies of this condition. Of particular interest is the observation that an antimicrobial agent, co-trimoxazole, has a protective effect in this model. The implication is that colonic bacteria play a critical role in carrageenan induced ulcerative colitis. However, studies to date have failed to specify which organisms are responsible for this effect or to define the nature of the carrangeenan-bacterial interaction. We propose to investigate the microbiology of ulcerative colitis using the carrageenan model in mice. These studies will employ advanced anaerobic bacteriological methods. Initial work will attempt to correlate dietary modifications, selective antimicrobial treatment and colonic flora studies with colitis production. Germfree animals will also be administered carrageenan to determine the effect of monocontamination with viable colonic bacteria; these results will be compared with the use of cell-free bacterial extracts. Finally, salicylazosulfapyridine will be tested to distinguish whether the activity of this agent resides in the antiinflammatory or the antimicrobial moiety. The intention of these studies is to identify specific bacteria responsible for carrageenan induced ulcerative colitis and to define the mechanism of bacterial activity. The ultimate goal is to determine the etiology of ulcerative colitis in order to apply the lessons to future studies in man.